Topic 12 - Antimicrobial Drugs

Who discovered the first "magic bullet" that selectively killed Treponema pallidum (syphilis)?

Paul Ehrlich

What is empirical therapy?

Starting antibiotic treatment before identifying the pathogen

What is targeted therapy?

Using a specific drug once the pathogen has been identified

What is synergism in antimicrobial therapy?

When two drugs work better together than alone

What does selective toxicity mean?

The drug kills or inhibits microbes without harming the host

Why are antibacterial drugs more common than antiviral or antifungal drugs?

Because bacteria have unique targets not found in human cells

Which drug class inhibits peptidoglycan cross-linking by binding PBPs?

β-lactams (Penicillin, Cephalosporins, Carbapenems)

What enzyme provides resistance by destroying the β-lactam ring?

β-lactamase

What does vancomycin inhibit?

Cross-linking between D-Ala-D-Ala subunits in peptidoglycan

What does bacitracin inhibit?

Transport of NAM and NAG out of the cytoplasm by binding bactoprenol

Which drugs inhibit mycolic acid synthesis in Mycobacterium?

Isoniazid and Ethambutol

Peptidoglycan is found in which type of organism?

Bacteria

Which drugs disrupt bacterial membranes by binding to LPS in Gram− bacteria?

Polymyxins (B and E)

Which drug depolarizes Gram+ bacterial membranes?

Daptomycin

Which antifungal drugs bind ergosterol and cause leakage?

Amphotericin B and Nystatin

Which class inhibits the 30S ribosomal subunit by causing mRNA misreading?

Aminoglycosides (Streptomycin, Gentamicin)

Which class inhibits the 30S ribosomal subunit by blocking tRNA binding?

Tetracyclines (Doxycycline, Minocycline)

Which class inhibits the 50S subunit by blocking ribosome movement?

Macrolides (Erythromycin, Azithromycin)

Which class inhibits peptide bond formation at the 50S subunit?

Chloramphenicol

Which class blocks initiation of translation at the 50S subunit?

Oxazolidinones (Linezolid)

Which class of antibiotics inhibits DNA gyrase or topoisomerase?

Fluoroquinolones (Ciprofloxacin)

Which class inhibits bacterial RNA polymerase?

Rifamycins (Rifampin)

Which drug class acts as a PABA analog to block folic acid synthesis?

Sulfonamides

Which drug blocks the later step in folate metabolism?

Trimethoprim

Why don't sulfa drugs affect humans?

Humans obtain folic acid from diet rather than synthesizing it

What is the common synergistic combination used to treat UTIs?

Trimethoprim + Sulfamethoxazole (Bactrim)

Which antiviral blocks fusion of HIV with the host cell?

Enfuvirtide

Which antiviral blocks uncoating of Influenza A virus?

Amantadine or Rimantadine

Which antiviral drug inhibits DNA polymerase in HSV infections?

Acyclovir

Which antiviral blocks reverse transcriptase in HIV?

Zidovudine (AZT)

Which antiviral blocks viral release in Influenza?

Oseltamivir (Tamiflu)

Which antifungal drug binds ergosterol to form membrane pores?

Amphotericin B

Which class of antifungals inhibits ergosterol synthesis?

Azoles (Fluconazole, Ketoconazole)

Which antifungal class inhibits β-glucan synthesis in fungal cell walls?

Echinocandins (Caspofungin)

Which antifungal interferes with mitosis in fungi?

Griseofulvin

Metronidazole

Flagyl

Chloroquine and Artemisinin

Antimalarial drugs that interfere with heme detoxification

Sulfadiazine + Pyrimethamine

Drug combination that treats Toxoplasma gondii and Cryptosporidium infections

β-lactamase

Enzyme that gives bacteria resistance to penicillin

Efflux pumps

Transport proteins that expel antibiotics from bacterial cells

Altered target site

Type of resistance that occurs when the drug target mutates

Biofilm

Structure that protects bacteria by reducing antibiotic penetration

Kirby-Bauer disk diffusion

Test that measures the zone of inhibition to determine sensitivity

MIC (Minimum Inhibitory Concentration)

Measures the lowest drug concentration that prevents visible growth

MBC (Minimum Bactericidal Concentration)

Measures the lowest concentration that kills bacteria

E-test

Test that combines qualitative and quantitative results using a gradient strip

Broad-spectrum antibiotics

Most appropriate when the pathogen is unknown (empirical therapy)

Narrow-spectrum antibiotics

Most appropriate when the pathogen is identified (targeted therapy)

Major disadvantage of broad-spectrum antibiotics

They kill normal flora and can cause superinfections

Intravenous (IV) or intramuscular (IM)

Route of administration that delivers drugs most rapidly

Polymyxin

Should not be given orally for systemic infections due to toxicity; used only topically

Tetracycline resistance mechanism

Bacteria use efflux pumps to actively transport tetracycline out of the cell, reducing its intracellular concentration

Most antifungal agents

Target the fungal cellular structure known as the cytoplasmic membrane

Allylamines and Azoles

Target the ergosterol synthesis pathway in the fungal membrane

Echinocandins

Target β-glucan synthesis in the fungal cell wall

Griseofulvin

Targets microtubules, inhibiting fungal mitosis

Polyenes such as Amphotericin B

Target ergosterol in the fungal cell membrane

Order for administration routes

1. Intramuscular; 2. Oral; 3. Intravenous

Acyclovir

Antiviral drug that mimics DNA nucleosides and inhibits viral replication, used to shorten herpes, chickenpox, and shingles infections

HIV Integrase Inhibitor (Raltegravir)

Prevents integration of viral DNA into the host genome

HIV Reverse Transcriptase Inhibitors (AZT, Tenofovir, Emtricitabine)

Inhibit viral reverse transcriptase enzyme, blocking RNA to DNA conversion

HIV Attachment/Entry Inhibitor (Maraviroc)

Blocks the CCR5 receptor on host cells to prevent viral entry

HIV Protease Inhibitors (Lopinavir, Nelfinavir)

Inhibit viral protease enzyme required for processing viral proteins

HIV Fusion Inhibitor (Enfuvirtide)

Prevents fusion of the viral envelope with the host cell membrane

Relenza and Tamiflu

Act to shorten the duration of Influenza by inhibiting release of the virus from infected cells